Disease/Drug of interest: Legionnaire's Disease and Moxifloxaacin
Motivation and Background:
Legionnaires Disease is a respiratory disease cause by the bacterium Legionella. Despite its exotic sounding name, Legionnaires Disease was not originally discovered in the Roman Legions or the French Foreign Legion, but rather at the domestic meeting of a veteran’s group, the American Legion. Legionnaires Disease primarily refers to the disease caused by Legionella pneumophilia, which results in an atypical pneumonia and accounts for over 90% of all Legionnaires cases. However, Legionnaires also refers to Pontiac Fever, a disease which is caused by some other species of Legionella, and it primarily resembles a case of acute influenza. Legionnaires is primarily spread through aerosolized water that contains the bacteria, and is not limited to any particular region. Legionella thrives in warm, humid environments, typically around 35˚ C. This means that the disease often thrives in air conditioning systems for large buildings, like the hotel that was hosting the meeting of the American Legion in which the disease was first discovered. Those infected with Legionnaires display many typical symptoms of pneumonia, such as fever, coughing up sputum, and coughing up bloody sputum. While Legionnaires is considered an easily treatable disease in developed areas of the world, developing regions lacking proper medical supplies, such as broad spectrum antibiotics, can find Legionnaires quite deadly.
References: 1. Ince, D.; Zhang, X.; Hooper, D. C., Activity of and resistance to moxifloxacin in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 2003, 47 (4), 1410-5. 2. Jonas, D.; Engels, I.; Friedhoff, C.; Spitzmüller, B.; Daschner, F. D.; Frank, U., Efficacy of moxifloxacin, trovafloxacin, clinafloxacin and levofloxacin against intracellular Legionella pneumophila. Antimicrobial Agents and Chemotherapy 2001, 47 (2), 147-52. 3. Schedletzky, H.; Wiedemann, B.; Heisig, P., The effect of moxifloxacin on its target topoisomerases from Escherichia coli and Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 1999, 43 Suppl B, 31-7. 4. Moxifloxacin (By Mouth). http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011288/?report=details
Moxifloxacin is a quinolone, a type of broad-spectrum antibiotic that targets topoisomerases and prevents DNA from winding properly [1]. Moxifloxacin in particular targets bacterial topoisomerase II, also commonly known as DNA gyrase, and topoisomerase IV [3]. DNA gyrase is the target of a great deal of antibiotics, especially quinolones. Gyrase allows the bacteria to supercoil DNA, or relax positively supercoiled DNA. In replication, gyrase is used to maintain tension in the helix prior to the replication fork. In this way, DNA gyrase is essential to the life cycle of a cell. Topoisomerase IV shares similar functions to DNA gyrase, but is also able to unlink DNA strands that become intertwined during replication. While both prokaryotes and eukaryotes have DNA gyrase, only bacteria have topoisomerase IV as well.
Legionella lives primarily in the respiratory tracts of infected humans, after the aerosolized water, or occasionally, soil, is inhaled. It operates by waiting in the respiratory tract until consumed by a macrophage (commonly known as a white blood cell). While within the macrophage, it blocks the connection of the phagosome (which contains the consumed bacteria) with the lysosome (containing the degradation materials), which allows it to replicate within the phagosome, until the macrophage bursts apart and releases the bacteria.
Size: molecular weight of the protein ~ 374 kDa
Location: Cytoplasmic
Function in a normal cell: Enable DNA replication
Drug Information:
Moxifloxacin (C21H24FN3O4, Molecular Weight: 403.431 g/mol, CAS: 354812-41-2) is a synthetic antibacterial commonly known as Avelox [4] and was originally patented by Bayer AG in 1989. In 1999, it was approved by the FDA for use on humans. There have been no clinical trials that specifically involve Legionnaires Disease and Moxifloxacin. It is also known as Avalox and Avelon. Moxifloxacin is most commonly prescribed orally, as a tablet. However, it is also available as an IV injection and as an eye drop. As with most other quinolones, it is a fluoroquinolone and is a broad spectrum antibiotic, acting against both Gram-negative and Gram-positive bacteria.
Moxifloxacin targets the DNA gyrase and topoisomerase of bacteria, interfering with their ability to bind to DNA and prevent positive supercoiling [2]. It is a highly effective antibiotic and is generally prescribed when strong intracellular penetration is required. In direct competition with this drug are most of the other quinolones, such as ciprofloxin, gemifloxacin,, levofloxacin, norfloxacin, and ofloxacin, as they serve very similar purposes with similar mechanisms of actions. Also, in addition to Legionnaires Disease, moxifloxacin is also commonly used on many other bacterial infections, particularly Staphylococcus pneumonia. Fluoroquinolones occasionally result in tendon rupture, tendonitis, peripheral neuropathy, and hepatitis.
Schematic figure of drug:
Formula: C21H24FN3O4
Molecular weight: 403.431 g/mol
CAS Number: 354812-41-2 Delivery method: Oral tablet, IV, eyedrop Side effects: Tendonitis and tendon rupture.
Also nausea, diarrhea, dizziness, lightheadedness, headache, weakness, trouble sleeping.
Other names: Avelox, Avelon Maker or company: Bayer AG Is it patented? Yes Clinical Trials Info: There are no clinical trials that involve Legionnaire's and Moxifloxacin, but Moxifloxacine has been used with many other infections as a broad spectrum antibiotic.
Origin:
Synthetic Alternatives to this drug: Most broad-spectrum antibiotics Miscellaneous: Other uses: can this drug be used to treat other diseases/conditions? Yes, as it is just a broad spectrum antibiotic.
Disease/Drug of interest: Legionnaire's Disease and Moxifloxaacin
Motivation and Background:
Legionnaires Disease is a respiratory disease cause by the bacterium Legionella. Despite its exotic sounding name, Legionnaires Disease was not originally discovered in the Roman Legions or the French Foreign Legion, but rather at the domestic meeting of a veteran’s group, the American Legion. Legionnaires Disease primarily refers to the disease caused by Legionella pneumophilia, which results in an atypical pneumonia and accounts for over 90% of all Legionnaires cases. However, Legionnaires also refers to Pontiac Fever, a disease which is caused by some other species of Legionella, and it primarily resembles a case of acute influenza. Legionnaires is primarily spread through aerosolized water that contains the bacteria, and is not limited to any particular region. Legionella thrives in warm, humid environments, typically around 35˚ C. This means that the disease often thrives in air conditioning systems for large buildings, like the hotel that was hosting the meeting of the American Legion in which the disease was first discovered. Those infected with Legionnaires display many typical symptoms of pneumonia, such as fever, coughing up sputum, and coughing up bloody sputum. While Legionnaires is considered an easily treatable disease in developed areas of the world, developing regions lacking proper medical supplies, such as broad spectrum antibiotics, can find Legionnaires quite deadly.
References:1. Ince, D.; Zhang, X.; Hooper, D. C., Activity of and resistance to moxifloxacin in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 2003, 47 (4), 1410-5.
2. Jonas, D.; Engels, I.; Friedhoff, C.; Spitzmüller, B.; Daschner, F. D.; Frank, U., Efficacy of moxifloxacin, trovafloxacin, clinafloxacin and levofloxacin against intracellular Legionella pneumophila. Antimicrobial Agents and Chemotherapy 2001, 47 (2), 147-52.
3. Schedletzky, H.; Wiedemann, B.; Heisig, P., The effect of moxifloxacin on its target topoisomerases from Escherichia coli and Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 1999, 43 Suppl B, 31-7.
4. Moxifloxacin (By Mouth). http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011288/?report=details
External links:
https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Datasheet/3/d0690dat.pdfTarget Information:
Moxifloxacin is a quinolone, a type of broad-spectrum antibiotic that targets topoisomerases and prevents DNA from winding properly [1]. Moxifloxacin in particular targets bacterial topoisomerase II, also commonly known as DNA gyrase, and topoisomerase IV [3]. DNA gyrase is the target of a great deal of antibiotics, especially quinolones. Gyrase allows the bacteria to supercoil DNA, or relax positively supercoiled DNA. In replication, gyrase is used to maintain tension in the helix prior to the replication fork. In this way, DNA gyrase is essential to the life cycle of a cell. Topoisomerase IV shares similar functions to DNA gyrase, but is also able to unlink DNA strands that become intertwined during replication. While both prokaryotes and eukaryotes have DNA gyrase, only bacteria have topoisomerase IV as well.Legionella lives primarily in the respiratory tracts of infected humans, after the aerosolized water, or occasionally, soil, is inhaled. It operates by waiting in the respiratory tract until consumed by a macrophage (commonly known as a white blood cell). While within the macrophage, it blocks the connection of the phagosome (which contains the consumed bacteria) with the lysosome (containing the degradation materials), which allows it to replicate within the phagosome, until the macrophage bursts apart and releases the bacteria.
Size: molecular weight of the protein ~ 374 kDa
Location: Cytoplasmic
Function in a normal cell: Enable DNA replication
Drug Information:
Moxifloxacin (C21H24FN3O4, Molecular Weight: 403.431 g/mol, CAS: 354812-41-2) is a synthetic antibacterial commonly known as Avelox [4] and was originally patented by Bayer AG in 1989. In 1999, it was approved by the FDA for use on humans. There have been no clinical trials that specifically involve Legionnaires Disease and Moxifloxacin. It is also known as Avalox and Avelon. Moxifloxacin is most commonly prescribed orally, as a tablet. However, it is also available as an IV injection and as an eye drop. As with most other quinolones, it is a fluoroquinolone and is a broad spectrum antibiotic, acting against both Gram-negative and Gram-positive bacteria.Moxifloxacin targets the DNA gyrase and topoisomerase of bacteria, interfering with their ability to bind to DNA and prevent positive supercoiling [2]. It is a highly effective antibiotic and is generally prescribed when strong intracellular penetration is required. In direct competition with this drug are most of the other quinolones, such as ciprofloxin, gemifloxacin,, levofloxacin, norfloxacin, and ofloxacin, as they serve very similar purposes with similar mechanisms of actions. Also, in addition to Legionnaires Disease, moxifloxacin is also commonly used on many other bacterial infections, particularly Staphylococcus pneumonia. Fluoroquinolones occasionally result in tendon rupture, tendonitis, peripheral neuropathy, and hepatitis.
Schematic figure of drug:
Formula:
C21H24FN3O4
Molecular weight:
403.431 g/mol
CAS Number:
354812-41-2
Delivery method: Oral tablet, IV, eyedrop
Side effects: Tendonitis and tendon rupture.
Also nausea, diarrhea, dizziness, lightheadedness, headache, weakness, trouble sleeping.
Other names: Avelox, Avelon
Maker or company: Bayer AG
Is it patented? Yes
Clinical Trials Info: There are no clinical trials that involve Legionnaire's and Moxifloxacin, but Moxifloxacine has been used with many other infections as a broad spectrum antibiotic.
Origin:
Synthetic
Alternatives to this drug: Most broad-spectrum antibiotics
Miscellaneous:
Other uses: can this drug be used to treat other diseases/conditions?
Yes, as it is just a broad spectrum antibiotic.